Platelet membrane-coated Prussian blue nanoparticles alleviated myocardial ischemia-reperfusion injury-induced cardiac dysfunction and adverse ventricular remodeling by disrupting PANoptosome assembly.
Platelet membrane-coated Prussian blue nanoparticles concurrently suppress pyroptosis, apoptosis, and necroptosis, providing a novel nanotherapeutic strategy for mitigating myocardial ischemia-reperfusion injury.
Abstract The extensive crosstalk among pyroptosis, apoptosis, and necroptosis limits the efficacy of therapies targeting only one pathway. Here, we show that Prussian blue (PB) nanoparticles act as multi-target PANoptosis inhibitors by binding key PANoptosome components including RIPK1, ZBP1, and AIM2 through multimodal interactions, thereby concurrently suppressing pyroptosis, apoptosis, and necroptosis in myocardial ischemia-reperfusion injury (MIRI). Platelet membrane-coated PB nanoparticles (PB@PM) exhibit enhanced cardiac targeting and efficiently alleviate MIRI-induced cardiac dysfunction, adverse ventricular remodeling, and cardiomyocyte hypertrophy. Mechanistically, PB@PM disrupt PANoptosome assembly, scavenge reactive oxygen species, improve mitochondrial function, and restore immune-inflammatory homeostasis. By integrating single nucleus transcriptomics of human heart samples, molecular dynamics simulations, transcriptomics, medical imaging, and molecular validation, we systematically decipher the therapeutic mechanisms of PB-based PANoptosis inhibition. This study establishes an integrative multi-omics framework for exploring PANoptosis in cardiovascular diseases and provides a promising nanotherapeutic strategy for MIRI treatment.
Xu et al. (Fri,) conducted a other in Myocardial ischemia-reperfusion injury. Platelet membrane-coated Prussian blue nanoparticles (PB@PM) vs. Prussian blue nanoparticles (PB) or MIRI control was evaluated on Cardiac function and infarct size. Platelet membrane-coated Prussian blue nanoparticles alleviated myocardial ischemia-reperfusion injury-induced cardiac dysfunction and adverse ventricular remodeling by disrupting PANoptosome assembly.